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Gennaro D’Amato

Direttore UOC di Malattie Respiratorie e Allergiche Dipartimento di Malattie Respiratorie

Azienda Ospedaliera ad alta Specialitàdi Rilievo Nazionale A. Cardarelli

Napoli Responsabile Area Clinica Associazione Italiana di

Pneumologia (AIPO)

Chairman World Allergy Organization Committee on Climate Change and Allergic Respiratory Diseases

Istituto Superiore di SanitàRoma 27-29 Maggio 2013

Variazioni climatiche , Variazioni climatiche , Inquinamento atmosfericoInquinamento atmosferico

e patologie respiratorie allergichee patologie respiratorie allergiche

AirPollution and Climate ChangeChanges in mean climatic conditions Increased variability, including extreme weather events

and heat waves

Glacierloss, sea-level rise

Altered surfacewater

Relocationof people

Communityand family

morale;mentalhealth

problems

Nutrition;child devel-

opment(and life-

course adulthealth)

Hygiene,homegrown

food

Microbialecology

hostanimals,vectors,

pathogenmultipli-cation)

Physicalhazards, risk

of death

Freshwater

availability

Foodprices andavailability

Injury,death, posteven traumatic stress and disease risk

Tourismand

recreation

Propertyloss

Ecosystemdamage

Reduced food

yields

Conflicts,displacement

Infra-structuredamage

Primary Environrnental and Social lmpactsDirect Health Impacts

Shortages,PriceChanges

Infectious-disease

risks

Indirect Health Impacts

Depressionafter event

Other systemic environmental changes acting and interacting

with climate change

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Am J Respir Crit Care Med 2000Am J Respir Crit Care Med 2000

• A.Increased mortality

• B.Increased incidence of cancer.

• C.Increased incidence of lower respiratory tract infections.

• D.Increased exacerbations of diseases in persons with chronic cardiopulmonary or other diseases:

- less able to cope with daily activity;

- increased hospitality (both frequency and duration);

- increased emergency ward or physician visits;

- increased pulmonary medications;

- decreased pulmonary functions.

• E.increased frequency of symptomatic asthmatic attacks

Adverse Respiratory Health Effects of Air Pollution

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Pyramid of respiratory effects of air pollution

Short-term vs. long-term effects

A continuumbetween?

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Is there a relationship between outdoor, indoor and personal exposure to air pollutants ?

PM 2.5

VOCs

EC

PAHs

� In 1992 in China there were 600.000 cars.

� In the year 2000 there were about 3.000.000 cars.

� It is forecasted that in the year 2010 there will be more than 20.000.000 vehicles on the roads of China.

(Dublin 2004 European Conference on Environment)

E invece già nel 2007 c’erano oltre 30.000.000 veicoli in Cina

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Studies done in USA, South America, Europe and Asia

•• Longitudinal studiesLongitudinal studies-- Frischer et al, AJRCCM 1999; 160: 390Frischer et al, AJRCCM 1999; 160: 390-- Jedrychowski et al, Environ Health Perspect 1999; 107: 669Jedrychowski et al, Environ Health Perspect 1999; 1 07: 669-- Hovak et al, Eur Respir J 2002; 19: 838Hovak et al, Eur Respir J 2002; 19: 838-- Gauderman et al, AJRCCM 2000; 162: 1383Gauderman et al, AJRCCM 2000; 162: 1383-- Avol et al, AJRCCM 2001; 164: 2067Avol et al, AJRCCM 2001; 164: 2067

•• Cross sectional studiesCross sectional studies-- Ware et al, ARRD 1986; 133: 834Ware et al, ARRD 1986; 133: 834-- Dockery et al, Environ Health Perspect 1996; 104: 506Dockery et al, Environ Health Perspect 1996; 104: 5 06-- Peters et al, AJRCCM 1999; 159: 768Peters et al, AJRCCM 1999; 159: 768

AMBIENT AIR POLLUTION AND LUNG FUNCTION DECREMENTS IN CHILDREN

Wong GW,Clin Exp Allergy 2001 Sunyer J, Thorax 1997

Anderson HR, Thorax 1998 Sunyer J, Occup Environ Med 2003

Lin M, Am J Epidemiol 2004

Correlazioni tra ricoveri ospedalieri per riacutizzazioni asmatiche e livelli di inquinamento atmosferico

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PuzzleSuscettibilità genetica

Allergeni

Infezioni, soprattutto virali

Infiammazione delle vie aeree ed iperreattività bronchiale

Fattori di Rischio di Allergia Respiratoria e di As ma

Agenti dell’inquinamento atmosferico sia esterno che interno (fumo di tabacco)

Farmaci come ASA

Esposizione occupazionale

Interazioni tra allergeni, agenti inquinanti ed infezioni.

Stile di vita

Attività fisica non adeguatamente protetta da farmaciStress

What May Play a Role inWhat May Play a Role in TodayToday´́s s Respiratory Allergy and Asthma?Respiratory Allergy and Asthma?

StressfulStressfulLifestyleLifestyle

NewNewAllergensAllergens

IndoorIndoorLifestyleLifestyle

Climate Climate Change Change

andandAir PollutionAir Pollution

PersistentPersistentallergenallergen

exposureexposure

PersistentPersistentsymptomssymptoms

AggressiveAggressiveallergensallergens

SevereSeveresymptomssymptoms

More andMore anddifferentdifferentallergensallergens

FrequentFrequentsymptomssymptoms

NeuroNeuro--immuneimmune

responsesresponses

SusceptiveSusceptiveto allergyto allergy

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( D’Amato G. Mediserve Ed. 2010)

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Total mass deposited

(mcg)

(Chalupa DC et al, Environ Health Perspect 2004 Jun e; 112: 879-882)

University of Rochester, New York

0

5

10

15

20

25

At rest exercise At rest exercise

Asthmatic subjects

Healthy

Particle deposition is higher in asthmatic subjects as compared to healthy subjects

Gennaro D’Amato

Director, Division of Respiratory and Allergic Dise asesDepartment of Chest Diseases

High Speciality Hospital A. CardarelliNapoli Italy

LondonVI WORLD Asthma and COPD Forum27- 30 April 2013

Air Pollution, Air Pollution, Climate Change Climate Change and Increasing prevalence and Increasing prevalence of Respiratory Allergyof Respiratory Allergy

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Air pollution

Outdoor

Indoor

The massive increase in emissions of air pollutants due to economic and industrial growthin the last century made air quality an environmental problem of first order in a largenumber of European and North American countries and it is now an emerging problem in other regions of the world.

There are 20 cities expected to have > 10 million inhabitantsThere are 20 cities expected to have > 10 million inhabitants by by the year 2015 and two thirds of mankind are expected to live in the year 2015 and two thirds of mankind are expected to live in megalopolis by 2020 megalopolis by 2020 Current projections suggest that the world population will be Current projections suggest that the world population will be close to nine billion by 2050close to nine billion by 2050

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In the last 50 years 50% of pluvial forestsof our Planet have been destroyed.

Each year 13 millions of forests ‘ hectaresare destroyed or deteriorated.

Each hour about 50 hectares of wood disappear.

Health Effects of Exposure to Ozone and PM2.5

• coughing• nose and throat irritation• chest pain• reduced lung function• increased susceptibility to respiratory illness

•aggravation of asthma • children with chronic lung disease

are particularly at risk

• increased risk of cardiac arrest and premature death

• aggravation of asthma• respiratory related hospital visits • reduced lung function and chronic

bronchitis• work and school absences• children with chronic lung disease

are particularly at risk

Ozone PM2.5

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1. Lung function decrements (Hazbun et al, AJRCCM2003).

2. Increased airway resistance (Seale et al, ARRD2003).

3. Altered airway permeability (Koren et al, Toxicol Pathol 2001).

4. Increased responsiveness to aeroallergens (Molfino et al, Lancet 1991; Peden et al, AJRCCM1995; Jorres et al, AJRCCM 2006).

5. Perturbation of antioxidant defences (Bolmberg et al, Eur Respir J 1999).

6. Airway neutrofilia (Schelegle et al, ARRD 2001; Stenfors et al, Respir Med 2008).

Human exposures to O 3 have been shown to elicit a spectrum of acute responses including:

Relationship between air pollution and asthma exacerbations in children

GL 2009

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McConnell et al observed that the incidence of new diagnoses of asthma in children are associated with heavy exercise in communities with high concentrations of ozone and PM. As a consequence, air pollution and outdoor exercise could contribute to the development of asthma in children.

McConnell R, Berhane K, Gilliland F et al.Asthma in exercising children exposed to ozone: a cohort study.Lancet 2002; 359: 386-391. McConnell R, Berhane K, Gilliland F et al.Prospective study of air pollution and bronchitic symptoms in children with asthma. AJRCCM 2003;168:790-797

Can air pollution induce a new-onset asthma ?

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Can air pollution induce a new-onset asthma ?

- Higher Allergenicity“There is an interaction between air pollutants and allergens

that exacerbates the development of atopy and the respiratory symptoms of allergic disease.” 1

- Higher Airway Responsiveness“In atopic subjects, exposure to air pollution inc reases airway

responsiveness to aeroallergens.” 1

- More Allergens“Increased ... air temperature significantly influe nces the

pollen production, .. and subsequent atmospheric po llen concentration” 1, 2, 3

Climate Change and Air Pollution lead to:

1 D‘Amato G et al. Eur Resp J 2002;Clin Exp Allergy 2005;Allergy 2007 ;Clin Exp Allerg y 2008,JIACI 2010

2 Ziska LH et al. J Allergy Clin Immunol. 2003.3 Cecchi L,D‘Amato G et al Allergy 2010

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D’Amato & Cecchi, Clin Exp Allergy, 2008

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Current knowledge of effects of climate change on respiratory allergy is provided by epidemiological and experimental studies on the relationship between asthma and environmental factors, such as meteorological variables, airborne allergens and air pollution.

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ERS EAACI Task Force on Climate Change, Air Pollution and Respiratory Diseases

Sep; 65(9):1073-81 Allergy, 2010

Endorsed by EAACI and ERSTask force on “Climate change, air pollution and respiratory dieseases”Chairpersons: G.D’Amato and I.Annesi

•Global warming affects start, duration and intensity of pollen season•Air pollution is associated with mortality and morbidity for respiratory and cardiovascular diseases.•PM and ozone are aggravating factors of asthma and increase the effects of airborne allergens with different mechanisms.•Living near heavy traffic roads is associated with impaired respiratory health and lung development.•Subjects living in urban areas tend to be more affected by plant-derived respiratory disorders than those living in rural area

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Climate Change, Migration and Allergic Respiratory Diseases D’Amato Gennaro and Menachem Rottem White Book of World Allergy Organization

WAO Committee on Climate Change and Allergic Diseases.

Chairman: G. D’Amato

WAO journal, July 2011

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de Marco R. et al.:de Marco R. et al.: The impact of The impact of climate climate and trafficand traffic--related NOrelated NO 2 2 on the on the prevalence of asthma and allergic prevalence of asthma and allergic rhinitis in Italy. rhinitis in Italy. Clin. Exp. Allergy 2002; 32: 1405Clin. Exp. Allergy 2002; 32: 1405--1412.1412.

D’Amato G.:D’Amato G.: Editorial: Outdoor air Editorial: Outdoor air pollution, climate and allergic pollution, climate and allergic respiratory diseases: evidence of a respiratory diseases: evidence of a link.link.Clin. Exp. Allergy 2002; 32:Clin. Exp. Allergy 2002; 32: 13911391--13931393

Climate interacts with outdoor exposure to NOClimate interacts with outdoor exposure to NO2 2 increasing the increasing the risk for allergic rhinitis and asthma in people exposed to high risk for allergic rhinitis and asthma in people exposed to high stable temperature.stable temperature.

There is hypothesis that air pollutants promote airway sensitizationby inducing changes in the allergenic content of airborne particles

carrying antigens such as pollens.

Gauderman WJ et al NEJM 2004; Behrendt H et al. Int Arch Allergy Immunol 1992Behrendt H et al. Int Arch Allergy Immunol 1992D’Amato G et al Eur Resp J 2002;Clin Exp Allergy 2005

Today’s allergens are particularly Today’s allergens are particularly aggressiveaggressive

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Emberlin et al CEA 1999;Emberlin et al CEA 1999;Beggs CEA 2002;Beggs CEA 2002;D’Amato et al ERJ2002; Allergy2007; CEA2008; JIACI 2010 D’Amato et al ERJ2002; Allergy2007; CEA2008; JIACI 2010

The plants flower earlier in urban areas than in the corresponding rural areas with earlier pollination

of about 2-4 days

The “urban climate effect”

A doubling of the A doubling of the atmospheric atmospheric CO2CO2 concentration stimulated concentration stimulated

ragweedragweed--pollen production by 61%pollen production by 61%

Production of allergenic pollen by ragweed ( Ambrosia artemisiifolia ) is

increased in CO2 enriched atmospheres

Wayne P. et al Ann Allergy Asthma Immunol. 2002

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Brunekreef et al, Lancet, 2000

“In a time-series study in the Netherlands, we found a strong association between the day-to-day variation in pollen concentrations and that of deaths due to cardiovascular disease, chronic obstructive pulmonary disease, and pneumonia”

Relation between airborne pollen Relation between airborne pollen concentrations and daily cardiovascular and concentrations and daily cardiovascular and

respiratoryrespiratory--disease mortalitydisease mortality

Poaceae Betula and Rumex weekly concentrations were positively associated to mortality

ResultsResults

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NAD(P)H= nicotinamide adenine dinucleotide phosphate oxidase,

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•• 19501950--1960 New Orleans 1960 New Orleans

•• 19701970--1980 Cartagena e Barcellona1980 Cartagena e Barcellona

•• 19811981--1987 1987 –– 26 nuovi episodi a Barcellona26 nuovi episodi a Barcellona

•• 1993 Napoli1993 Napoli

Fattori meteorologici Fattori meteorologici (direzione del vento, (direzione del vento,

inversione termica, ecc.)inversione termica, ecc.)

“cluster” di gravi crisi di asma con evidenza anatomo-patologica (nei morti) di un meccanismo di tipo “anafilattico”

Dispersione atmosferica della polvere dei silos

portuali

Crisi epidemiche di asma da soia

Pollen fragments

Starch granules and other cytoplasmic granules

Non-pollen plant parts (from inflorescences, leaves orUbisch bodies)

Non-plant particulate matter (allergens transferredthrough physical contact or by leaching from thesurface of the pollen grain to other airborne smallparticles).

Climate Changes favour production also of Airborne Small Allergen-carrying Particles

D’Amato G et al Allergy 2007; Clin Exp Allergy 2008 ; JIACI 2010;ERR 2012

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The potential role of orbiculesThe potential role of orbicules(Ubish bodies) (Ubish bodies)

as vector of allergens.as vector of allergens.

D’Amato G D’Amato G -- Z Erkrank Atm Org 1981Z Erkrank Atm Org 1981Pacini E Franchi GG Pacini E Franchi GG -- Plant Syst Evol 1993Plant Syst Evol 1993Vinckier S Smets E Vinckier S Smets E -- Allergy 2001Allergy 2001D’Amato G D’Amato G -- Allergy 2001Allergy 2001D’Amato G et al Clin Exp Allergy 2005D’Amato G et al Clin Exp Allergy 2005D’Amato G et al Allergy 2007;JIACI 2010D’Amato G et al Allergy 2007;JIACI 2010

Changes are also occurring in the amount, intensity , frequency and type of precipitation as well as the increase of ex treme events, like

heat waves, droughts, floods and hurricanes

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Packe GE, Ayres JG Asthma outbreak during a thunder storm. Lancet 1985; ii: 199-204

Association between a thunderstorm and an asthma ou tbreak with 26 asthmatic subjects treated in Birmingham Hospital i n 36 hours compared with 2-3 cases in the same time in the days precedi ng the thunderstorm.

London 25 June 1994

Celenza A et al. Thunderstorms associated asthma: A detailed analysis of environmental factors. BMJ 1996;312:604-607

Thames Regions Accident and Emergency Trainer Association. A major outbreak of asthma associated with a thunderstorm: experience of accident and emergency departments and patients characteristics BMJ 1996;312:601-4

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Bellomo R et al. Two consecutive thunderstorm associated epidemics of Bellomo R et al. Two consecutive thunderstorm associated epidemics of asthma in Melbourne. asthma in Melbourne. Med J Aust 1992; 156: 834Med J Aust 1992; 156: 834--77

Also this phenomenon was followed by a rapid increa se in hospital or general practitioner visits for asthma.No unusual levels of air pollution were noted at th e time of these

epidemics but there was a strong association with g rass pollen.

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Napoli 4 June 2004 (D’Amato G et al Allergy 2007)Napoli 4 June 2004 (D’Amato G et al Allergy 2007)

7 patients received treatment in emergency departme nts and one was admitted to an intensive care unit for acute respiratory ins ufficiency.

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Under wet conditions or during thunderstorms pollen grains may, after rupture by osmotic shock, release part of their cytoplasmic content into the atmosphere.

Thunderstorm related epidemics of rhinitis and asthma exacerbations

D’Amato G, et al BMJ 2005; ClinExpAllergy2005;Allergy 2007;JACI2008;JIACI2010

The extraordinarily long persistence in the atmosph ere of Parietaria pollen in Mediterranean area is responsible for a multiseasonal symptomato logy .

31/05/200402/06/2004

04/06/200406/06/2004

0

20

40

60

80

100

120

140

160

polle

n gr

ains

URTICACEAE

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The pollinic allergens are locatedThe pollinic allergens are locatedThe pollinic allergens are locatedThe pollinic allergens are locatedin the walls or in the cytoplasmin the walls or in the cytoplasmin the walls or in the cytoplasmin the walls or in the cytoplasm

Orbiculs

Intine

-cytoplasm-R.E.-Nucleous-plastids

Hydrated pollen on a wet surface

starch

lipid dropsproteins

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Pollen grains fragmented and dispersed in atmospher e

Marks G.B. et al. Thorax 2001; 56:468-471“the arrival of a thunderstorm was accompanied by a large increase in the concentration of ruptured pollen grains”

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D’Amato G et al. J Allergy Clin Immunol 2008;121:537-38

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D’Amato G et al.- Environmental risk factors and all ergic bronchial asthma. Clin Exp Allergy 2005;35:1113-112 4.

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28 Maggio 2012 ore 12.48

D’Amato G et al. Eur Ann Allergy Clin Immunol 20 13 (In press)

A young lady who experienced near fatal asthma in c oncomitance with a thunderstorm in June 2004 was admitted againin the emergency room department of Cardarelli hos pital in Naples on 24 May 2011 and on 28 May 2012 for other two at tacks of near fatal asthma (the last, in 2012, in pregnancy).

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Although thunderstorm-associated asthma outbreaks a re not frequent, it is possible to observe in clinical practice single cases of patients with deterioration of the allergic respiratory symptoms during a thunderstorm.

There is a role for cold or thunderbolts and electricity in atmosphere?

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1) The occurrence of epidemics is closely linked to thunderstorm

2) The thunderstorm related epidemics are limited to late spring and summer when there are high levels of airborne polle n grains

3) There is a close temporal association between th e arrival of the thunderstorm, a major rise in the concentration of pollen grains and the onset of epidemics

4) Subjects with pollen allergy, who stay indoors wi th window closed during thunderstorm, are not involved

5) There is a major risk for subjects who are not under antiasthma correct treatment, but subjects with allergic rhini tis and without previous asthma can experience severe bronchoconstr iction.

The evidence about thunderstorm related The evidence about thunderstorm related epidemics of rhinitis and asthma exacerbations:epidemics of rhinitis and asthma exacerbations:

Take home message:Subjects affected by pollen allergy should be alert to the Subjects affected by pollen allergy should be alert to the danger of being outdoors during a thunderstorm in the danger of being outdoors during a thunderstorm in the

pollen season.pollen season.

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D’Amato G, et alFacebook. A new trigger for asthma?The Lancet, Vol 376;Nov20,2010 p1740

76 Millions of tons of CO2 produced by Internet in 200276 Millions of tons of CO2 produced by Internet in 2002700700 Millions of tons in 2012Millions of tons in 2012

D’Amato G, et alSocial Networks : a new source of psychological stress or a wayto enhance self-esteem? Negative and positive implicationsin bronchial asthma. JIACI 2012

D’Amato G, Cecchi L, Social Networks and bronchial asthma.Curr Opin Allergy Clin Immunol.Feb 13 (1) 87-91;2013

Decreasing use of fossil fuels and controlling vehicle emissions.

Reducing the private traffic in towns.

Improving the public transport.

Planting in cities non-allergenic trees.

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•• ConclusioniConclusioni: In pazienti con asma severo : In pazienti con asma severo refrattario alla terapia, il soggiorno in refrattario alla terapia, il soggiorno in altitudine migliora i parametri clinici e altitudine migliora i parametri clinici e funzionali e riduce la richiesta di funzionali e riduce la richiesta di corticosteroidi, indipendentemente dalla corticosteroidi, indipendentemente dalla presenza di presenza di atopiaatopia

1.1. Basso livello di acari, spore fungine e polliniBasso livello di acari, spore fungine e pollini

2.2. Diretto beneficio fisiologico della bassa Diretto beneficio fisiologico della bassa viscosità dell’aria che riduce le resistenze viscosità dell’aria che riduce le resistenze respiratorierespiratorie

3.3. Riduzione dello stress psicologico e lavorativoRiduzione dello stress psicologico e lavorativo

4.4. Esposizione ad alti livelli di UV che stimolano la Esposizione ad alti livelli di UV che stimolano la produzione di vitamina D, modulando l’attività produzione di vitamina D, modulando l’attività del sistema immunitario del sistema immunitario

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Key messages

� Exacerbation of asthma (in asthmatic subjects)� Adjuvant effect on allergic sensitization� Possible induction of new onset asthma� Clinical effects determined by genetic susceptibility� Possible relationship with stress and socioeconomic deprivation� Possible effects for exposure during pregnancy and early-life� Possible reduction of the response to drugs

WAO Committee on

Climate Change and Allergic Diseases

ERS EAACI Task Force on Climate Change, Air Pollution and

Respiratory Diseases

Strategies to reduce climate changes and air pollution arepolitical in nature, but citizen and in particular healthprofessionals and societies must raise their voices in thedecision process to give strong support for clean policies o nboth national and international levels.

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Inquinamento atmosferico, variazioni climatiche e patologie

respiratorie, AIPO 2012

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ThanksThanksgdamatomail@gmail.comgdamatomail@gmail.com

“Respiro Campania”“Respiro Campania”Gruppo su facebookGruppo su facebook

D’Amato G et al: Facebook: a new trigger for asthma? The Lancet 2010, 376: 1740

D’Amato G. et al: Social Networks: A New Source of Psychological Stress or a Way to Enhance Self-esteem? Negative and Positive Implications in Bronchial

Asthma. J Investig Allergol Clin Immunol 2012; Vol. 22(6): 402-405

D’Amato G et al: Social Networks and Bronchial Asthma. Current opinion in Allergy and Clinical Immunology 13(1): 87-91, February 2013

�Vi sono prove che, in alcuni pazientiasmatici, l'uso eccessivo dei social networkpuò indurre depressione e stress scatenanteostruzione bronchiale, mentre in altri il lorouso razionale può indurre effetti benefici intermini di gestione della malattia.